Effects of a Novel Fixed Combination of Nutraceuticals on Serum Uric Acid Concentrations and the Lipid Profile in Asymptomatic Hyperuricemic Patients

Results from the PICONZ-UA Study

Abstract

Introduction

Asymptomatic hyperuricemia is not a current indication for therapy as the definite role of serum uric acid elevation as a cardiovascular risk factor is extremely likely but still controversial.

Aim

We designed a double blind, placebo-controlled, randomized study to assess the effects of a combination of nutraceuticals (ZinutriK®, containing a fixed combination of kampferol, baicalin, caffeine, and rutin) on serum uric acid levels, lipid variables and the global cardiovascular risk profile.

Methods

Sixteen individuals (mean age 59.0 ± 11.9 years, 4 women) with asymptomatic hyperuricemia completed the study.

Results

ZinutriK® treatment (4 weeks) reduced serum uric acid concentrations (from 7.9 + 0.9 to 7.0 + 0.7 mg/dL) when compared to both baseline and placebo (p < 0.006 and p < 0.001, respectively). Compared to both placebo and baseline, the same fixed combination of nutraceuticals also reduced circulating LDL cholesterol and increased HDL cholesterol concentrations within 4 weeks (p < 0.001 or less), thereby improving the Framingham risk score (p < 0.001 or less). Neither minor nor major side effects were observed.

Conclusions

This study represents the first demonstration that a short-term therapy with a fixed combination of different natural substances can significantly reduce serum uric acid concentrations in asymptomatic hyperuricemic patients, with no side effects and a significant improvement in the lipid pattern and then in the global cardiovascular risk profile.

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References

  1. 1.

    Ciarla S, Struglia M, Giorgini P, Striuli R, Necozione S, Properzi G, Ferri C. Serum uric acid levels and metabolic syndrome. Arch Physiol Biochem. 2014;120(3):119–22.

    CAS  Article  PubMed  Google Scholar 

  2. 2.

    Grassi D, Desideri G, Ferri C. New insight into urate-related mechanism of cardiovascular damage. Curr Pharm Des. 2014;20(39):6089–95.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    The Sixth Joint Task Force of the European. Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37(29):2315–81.

    Article  Google Scholar 

  4. 4.

    Palmer TM, Nordestgaard BG, Benn M, Tybjærg-Hansen A, Davey Smith G, Lawlor DA, Timpson NJ. Association of plasma uric acid with ischaemic heart disease and blood pressure: mendelian randomisation analysis of two large cohorts. BMJ. 2013;347: f4262.

  5. 5.

    Yang Q, Köttgen A, Dehghan A, Smith AV, Glazer NL, Chen MH, Chasman DI, Aspelund T, Eiriksdottir G, Harris TB, Launer L, Nalls M, Hernandez D, Arking DE, Boerwinkle E, Grove ML, Li M, Linda Kao WH, Chonchol M, Haritunians T, Li G, Lumley T, Psaty BM, Shlipak M, Hwang SJ, Larson MG, O’Donnell CJ, Upadhyay A, van Duijn CM, Hofman A, Rivadeneira F, Stricker B, Uitterlinden AG, Paré G, Parker AN, Ridker PM, Siscovick DS, Gudnason V, Witteman JC, Fox CS, Coresh J. Multiple genetic loci influence serum urate levels and their relationship with gout and cardiovascular disease risk factors. Circ Cardiovasc Genet. 2010;3(6):523–30.

  6. 6.

    Kleber ME, Delgado G, Grammer TB, Silbernagel G, Huang J, Krämer BK, Ritz E, März W. Uric acid and cardiovascular events: a mendelian randomization study. JASN. 2015;26(11):2831–8.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Savarese G, Ferri C, Trimarco B, Rosano G, Dellegrottaglie S, Losco T, Casaretti L, D’Amore C, Gambardella F, Prastaro M, Rengo G, Leosco D, Perrone-Filardi P. Changes in serum uric acid levels and cardiovascular events: a meta-analysis. Nutr Metab Cardiovasc Dis. 2013;23(8):707–14.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Silbernagel G, Hoffmann MM, Grammer TB, Boehm BO, März W. Uric acid is predictive of cardiovascular mortality and sudden cardiac death in subjects referred for coronary angiography. Nutr Metab Cardiovasc Dis. 2013;23(1):46–52.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    Thornley S, Marshall RJ, Jackson R, Gentles D, Dalbeth N, Crengle S, Kerr A, Wells S. Is serum urate causally associated with incident cardiovascular disease? Rheumatology. 2013;52(1):135–42.

    Article  PubMed  Google Scholar 

  10. 10.

    Kim SY, Guevara JP, Kim KM, Choi HK, Heitjan DF, Albert DA. Hyperuricemia and coronary heart disease: a systematic review and meta-analysis. Arthritis Care Res. 2010;62(2):170–80.

    Google Scholar 

  11. 11.

    Rho YH, Zhu Y, Choi HK. The epidemiology of uric acid and fructose. Semin Nephrol. 2011;31(5):410–9.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Johnson RJ, Sautin YY, Oliver WJ, Roncal C, Mu W, Gabriela Sanchez-Lozada L, Rodriguez-Iturbe B, Nakagawa T, Benner SA. Lessons from comparative physiology: could uric acid represent a physiologic alarm signal gone awry in western society? J Comp Physiol. 2009;179(1):67–76.

  13. 13.

    Jung MH, Seong PN, Kim MH, Myong NH, Chang MJ. Effect of green tea extract microencapsulation on hypertriglyceridemia and cardiovascular tissues in high fructose-fed rats. Nut Res Pract. 2013;7(5):366–72.

    CAS  Article  Google Scholar 

  14. 14.

    Sautin YY, Nakagawa T, Zharikov S, Johnson RJ. Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress. Am J Physiol. 2007;293(2):C584–96.

    CAS  Article  Google Scholar 

  15. 15.

    Anyachuckwu Irondi E, Olalekan Agboola S, Oboh G, Boligon AA, Athayde ML, Shode FO Guava leaves polyphenolics-rich extract inhibits vital enzymes implicated in gout and hypertension in vitro. J Intercult Ethnopharmacol. 2016;5(2):122–30.

  16. 16.

    Jang YJ, Kim J, Shim J, Kim J, Byun S, Oak MH, et al. Kaempferol attenuates 4-hydroxynonenal-induced apoptosis in PC12 cells by directly inhibiting NADPH oxidase. J Pharmacol. Exp. Ther. 2011;337(3):747–54.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Bochorakova H, Paulova H, Slanina J, Musil P, Taborska E. Main flavonoids in the root of Scutellaria baicalensis cultivated in Europe and their comparative antiradical properties. Phytother Res. 2003;17(6):640–4.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    D’Agostino RB Sr, Grundy S, Sullivan LM. Wilson P; CHD Risk Prediction Group. Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA. 2001;286(2):180–7.

    Article  PubMed  Google Scholar 

  19. 19.

    Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34(28):2159–219.

    Article  PubMed  Google Scholar 

  20. 20.

    Trimarco V, Izzo R, Stabile E, Rozza F, Santoro M, Manzi MV, et al. Effects of a new combination of nutraceuticals with Morus alba on lipid profile, insulin sensitivity and endotelial function in dyslipidemic subjects. A cross-over, randomized, double-blind trial. High Blood Press Cardiovasc Prev. 2015;22(2):149–54.

  21. 21.

    Izzo R, de Simone G, Giudice R, Chinali M, Trimarco V, De Luca N, et al. Effects of nutraceuticals on prevalence of metabolic syndrome and on calculated Framingham Risk Score in individuals with dyslipidemia. J Hypertens. 2010;28(7):1482–7.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Santos CX, Anjos EI, Augusto O. Uric acid oxidation by peroxynitrite: multiple reactions, free radical formation, and amplification of lipid oxidation. Arch Biochem Biophys. 1999;372(2):285–94.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Ciarla S, Giorgini P, Struglia M, Striuli R, Necozione S, Desideri G, et al. Associations between low levels of serum uric acid and cardiometabolic parameters. Arch Phys Biochem. 2015;121(4):139–43.

    CAS  Article  Google Scholar 

  24. 24.

    Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular risk. N Engl J Med. 2008;23,359(17):1811–21.

  25. 25.

    Kojima S, Matsui K, Ogawa H, Jinnouchi H, Hiramitsu S, Hayashi T, et al. Rationale, design, and baseline characteristics of a study to evaluate the effect of febuxostat in preventing cerebral, cardiovascular, and renal events in patients with hyperuricemia. J Cardiol. 2016. doi:10.1016/j.jjcc.2016.02.015.

    Google Scholar 

  26. 26.

    Kleijnen J, Knipschild P. Ginkgo biloba. Lancet. 1992;340(8828):1136–9.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Landes P. Market report: whole Foods magazine’s 2nd annual herb market survey for U.S. health food stores. Herbal Gram 1997:40–52.

  28. 28.

    Borghi C, Perez-Ruiz F. Urate lowering therapies in the treatment of gout: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2016;20(5):983–92.

    CAS  PubMed  Google Scholar 

  29. 29.

    Degli Esposti L, Saragoni S, Buda S, Desideri G, Borghi C. Retrospective analysis on hospitalization and health care costs, according to serum uric acid levels in patients from a sample of Italian local health units. Int J Soc Pharmacoecon Outcom Res. 2014;17(7):A477–8.

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Correspondence to Raffaele Izzo.

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Rozza, F., Trimarco, V., Izzo, R. et al. Effects of a Novel Fixed Combination of Nutraceuticals on Serum Uric Acid Concentrations and the Lipid Profile in Asymptomatic Hyperuricemic Patients. High Blood Press Cardiovasc Prev 23, 381–386 (2016). https://doi.org/10.1007/s40292-016-0168-x

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Keywords

  • Hyperuricemia
  • Nutraceuticals
  • Hyperlipidemia